Effect of interleukin-2 on cell proliferation, sister-chromatid exchange induction, and nuclear stress protein phosphorylation in PHA-stimulated Fischer 344 rat spleen lymphocytes: modulation by 2-mercaptoethanol.
The effect of interleukin-2 (IL-2) on cell proliferation, sister-chromatid exchange (SCE) frequency, and the phosphorylation of nuclear stress proteins was evaluated in phytohemagglutinin (PHA)-stimulated spleen lymphocytes isolated from Fischer 344 rats. In addition, the ability of 2-mercaptoethanol (2-ME) to modulate the induction of these biological responses was characterized. Cell proliferation, as measured by the mitotic index, increased significantly (P less than .003) from a range of 3-4% in PHA-stimulated cultures to a range of 8-11% in PHA-stimulated cultures exposed to IL-2. The average generation time (AGT) did not respond to IL-2 in a concentration-dependent manner and decreased significantly (P less than .05) when 20 microM 2-ME was included with IL-2 in the culture medium. The number of SCE increased significantly (P less than .004) from control frequencies, which ranged from 13.1 to 15.6 SCE per cell, to frequencies of 18.5 to 21.5 SCE per cell as the concentration of IL-2 in the culture medium increased to 50 half-maximal units per ml. A reduction in SCE frequency was observed when cells were cultured with 20 microM 2-ME and IL-2 compared to IL-2 alone. Three nuclear proteins, with relative molecular masses of approximately 13,000-18,000, 20,000, and 80,000, were phosphorylated in IL-2-exposed G1-phase nuclei. Elicitation of these nuclear proteins in IL-2-exposed cells was not affected by exposure to 2-ME.
Morris
S M
SM
Division of Genetic Toxicology, Food and Drug Administration, National Center for Toxicological Research, Jefferson, Arkansas 72079.
Aidoo
A
A
Domon
O E
OE
McGarrity
L J
LJ
Kodell
R L
RL
Schol
H M
HM
Hinson
W G
WG
Pipkin
J L
JL
Casciano
D A
DA
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003627:Data Interpretation, Statistical; D004347:Drug Interactions; D006360:Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008623:Mercaptoethanol / Q000494:pharmacology*; D008940:Mitotic Index / Q000187:drug effects; D009687:Nuclear Proteins / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D010835:Phytohemagglutinins / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D012854:Sister Chromatid Exchange / Q000187:drug effects; D013154:Spleen / Q000166:cytology / Q000187:drug effects
D006360:Heat-Shock Proteins; D007376:Interleukin-2; D009687:Nuclear Proteins; D010835:Phytohemagglutinins; D008623:Mercaptoethanol